Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy

Teepen, Jop C.; Leeuwen, Flora E. van; Tissing, Wim J. E.; Broeder, Eline van Dulmen‐den; Heuvel‐Eibrink, Marry M. van den; Pal, Helena J. van der; Loonen, Jacqueline J.; Bresters, Dorine; Versluys, Birgitta; Neggers, Sebastian J C M M; Jaspers, Monique W. M.; Hauptmann, Michael; Loo, Margriet van der Heiden‐van der; Visser, Otto; Kremer, Leontien C. M.; Ronckers, Cécile M.

doi:10.1200/jco.2016.71.6902

Cited by 179 publications

(231 citation statements)

References 46 publications

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“…For all cohort members, details on cancer diagnosis and treatment schedules were retrospectively obtained from medical records using a standardized protocol. Methods of patient identification and data collection have been previously described elsewhere …”

Section: Methodsmentioning

confidence: 99%

The involvement of primary care physicians in care for childhood cancer survivors

Streefkerk

Heins

Teepen

et al. 2019

Pediatric Blood & Cancer

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Background Childhood cancer survivors (CCS) are at risk of developing long‐term morbidity, which is likely to be presented to a primary care physician (PCP). Therefore, insight into CCS's PCP‐based health care use is needed. We investigated the volume and underlying health problems of PCP‐based health care use and the determinants for PCP‐based health care use in CCS. Procedure Data from a Dutch cohort of 6018 eligible five‐year CCS were linked to the Nivel Primary Care database, which contains detailed data from a representative sample of 10% of all Dutch PCPs. Per CCS, two matched controls were selected. Negative binomial regression was performed to compare the annual number of contacts between CCS and controls, and to identify determinants for PCP‐based care use among CCS. Results This study included 602 CCS and 1204 controls. CCS were 1.3 times more likely to contact their PCP than controls (95% CI, 1.2–1.5), up to 1.5 times at attained age over 40 years (95% CI, 1.2–1.8). CCS were 4.9 times more likely to contact their PCP for new malignancies, 3.1 for hematological conditions, and 2.8 for endocrine conditions. Female sex, higher attained age, and treatment with radiotherapy were determinants for having more PCP contacts. Conclusions PCPs play an important role in care for CCS. CCS use more PCP‐based care than matched controls, mainly for severe conditions such as malignancies, hematological, and endocrine conditions. Our results emphasize the importance of disseminating the current knowledge on long‐term morbidity in CCS and on their optimal follow‐up care among PCPs.

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Section: Methodsmentioning

confidence: 99%

The involvement of primary care physicians in care for childhood cancer survivors

Streefkerk

Heins

Teepen

et al. 2019

Pediatric Blood & Cancer

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“…Despite intensive therapy, prognosis is poor in patients with metastatic and relapsed disease . Moreover, patients who survive face debilitating and often life‐threatening health consequences as a result of the highly toxic therapy . There is an urgent need to identify novel opportunities for therapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

Svoboda

Teh

Sud

et al. 2018

The Journal of Pathology

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Developmental transcription programs are epigenetically regulated by multi-protein complexes, including the menin- and MLL-containing trithorax (TrxG) complexes, which promote gene transcription by depositing the H3K4me3 activating mark at target gene promoters. We recently reported that in Ewing sarcoma, MLL1 (lysine methyltransferase 2A, KMT2A) and menin are overexpressed and function as oncogenes. Small molecule inhibition of the menin-MLL interaction leads to loss of menin and MLL1 protein expression, and to inhibition of growth and tumorigenicity. Here, we have investigated the mechanistic basis of menin-MLL-mediated oncogenic activity in Ewing sarcoma. Bromouridine sequencing (Bru-seq) was performed to identify changes in nascent gene transcription in Ewing sarcoma cells, following exposure to the menin-MLL interaction inhibitor MI-503. Menin-MLL inhibition resulted in early and widespread reprogramming of metabolic processes. In particular, the serine biosynthetic pathway (SSP) was the pathway most significantly affected by MI-503 treatment. Baseline expression of SSP genes and proteins (PHGDH, PSAT1, and PSPH), and metabolic flux through the SSP were confirmed to be high in Ewing sarcoma. In addition, inhibition of PHGDH resulted in reduced cell proliferation, viability, and tumor growth in vivo, revealing a key dependency of Ewing sarcoma on the SSP. Loss of function studies validated a mechanistic link between menin and the SSP. Specifically, inhibition of menin resulted in diminished expression of SSP genes, reduced H3K4me3 enrichment at the PHGDH promoter, and complete abrogation of de novo serine and glycine biosynthesis, as demonstrated by metabolic tracing studies with C-labeled glucose. These data demonstrate that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley& Sons, Ltd.

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“…The survival of children with cancer has substantially improved over the last few decades; however, late effects have gained more importance. One of the most serious late effects is the occurrence of second malignant neoplasms (SMNs) . The characterization of treatment factors predisposing patients to the development of SMNs is important in identifying high‐risk groups, who may benefit from screening or preventative measures .…”

Section: Introductionmentioning

confidence: 99%

Risk of subsequent colorectal cancers after a solid tumor in childhood: Effects of radiation therapy and chemotherapy

Allodji

Haddy

Vu‐Bezin

et al. 2018

Pediatric Blood & Cancer

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Background Very few previous studies have addressed the question of colorectal cancer (CRC) after childhood cancer treatment. We aimed to quantify the roles of radiation therapy and chemotherapy agents in the occurrence of subsequent CRC. Methods A nested case–control study was conducted using 36 CRC cases and 140 controls selected from 7032 five‐year survivors of the French Childhood Cancer Survivor Study (FCCSS) cohort, treated from 1945 to 2000 in France. The radiation dose‐distribution metrics at the site of CRC and doses of individual chemotherapeutic agents were calculated. Conditional logistic regressions were performed to calculate odds ratios (ORs). Results Overall, patients who received radiotherapy with estimated dose to colon had a 4.3‐fold (95% CI, 1.3–17.6) increased risk for CRC compared with patients who did not receive radiotherapy, after adjustment for chemotherapy. This risk increased to 8.9‐fold and 19.3‐fold among patients who received radiation doses ranging from 20 to 29.99 Gy and ≥30 Gy, respectively. Our data reported a significantly elevated OR for anthracyclines, after controlling for radiotherapy and MOPP regimen. But, restricted analyses excluding patients who had received ≥30 Gy showed that only radiation doses ranging from 20 to 29.99 Gy produced a significant increase in subsequent CRC risk (OR = 7.8; 95% CI, 1.3–56.0), after controlling for anthracyclines and MOPP regimen. Conclusions The risk of subsequent CRC was significantly increased after radiation dose (even < 30 Gy). This novel finding supports the need to update monitoring guidelines for CRC to optimize the long‐term follow‐up for subsequent CRC in survivors of childhood cancer.

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Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy

Cited by 179 publications

References 46 publications

The involvement of primary care physicians in care for childhood cancer survivors

The involvement of primary care physicians in care for childhood cancer survivors

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

Risk of subsequent colorectal cancers after a solid tumor in childhood: Effects of radiation therapy and chemotherapy

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